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Phase I Trial of the Positron-Emitting Arg-Gly-Asp (RGD) Peptide Radioligand ¹⁸F-AH111585 in Breast Cancer Patients

¹ Department of Oncology, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom; ² GE Healthcare Medical Diagnostics, Amersham Place, Buckinghamshire, United Kingdom; and ³ Department of Nuclear Medicine, Imperial College Faculty of Medicine, Hammersmith Hospital, London, United Kingdom

Correspondence: For correspondence or reprints contact: Eric O. Aboagye, Room 242 MRC Cyclotron Building, Hammersmith Hospital, DuCane Rd., London W12 0NN, U.K. E-mail: eric.aboagye{at}imperial.ac.uk

The integrin _vβ₃ receptor is upregulated on tumor cells and endothelium and plays important roles in angiogenesis and metastasis. Arg-Gly-Asp (RGD) peptide ligands have high affinity for these integrins and can be radiolabeled for PET imaging of angiogenesis or tumor development. We have assessed the safety, stability, and tumor distribution kinetics of a novel radiolabeled RGD-based integrin peptide-polymer conjugate, ¹⁸F-AH111585, and its feasibility to detect tumors in metastatic breast cancer patients using PET. Methods: The biodistribution of ¹⁸F-AH111585 was assessed in 18 tumor lesions from 7 patients with metastatic breast cancer by PET, and the PET data were compared with CT results. The metabolic stability of ¹⁸F-AH111585 was assessed by chromatography of plasma samples. Regions of interest (ROIs) defined over tumor and normal tissues of the PET images were used to determine the kinetics of radioligand binding in tissues. Results: The radiopharmaceutical and PET procedures were well tolerated in all patients. All 18 tumors detected by CT were visible on the ¹⁸F-AH111585 PET images, either as distinct increases in uptake compared with the surrounding normal tissue or, in the case of liver metastases, as regions of deficit uptake because of the high background activity in normal liver tissue. ¹⁸F-AH111585 was either homogeneously distributed in the tumors or appeared within the tumor rim, consistent with the pattern of viable peripheral tumor and central necrosis often seen in association with angiogenesis. Increased uptake compared with background (P = 0.002) was demonstrated in metastases in lung, pleura, bone, lymph node, and primary tumor. Conclusion: ¹⁸F-AH111585 designed to bind the _vβ₃ integrin is safe, metabolically stable, and retained in tumor tissues and detects breast cancer lesions by PET in most anatomic sites.

Key Words: integrin • RGD • tumor • positron emission tomography • _vβ₃

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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				B. J. McParland, M. P. Miller, T. J. Spinks, L. M. Kenny, S. Osman, M. K. Khela, E. Aboagye, R. C. Coombes, A.-M. Hui, and P. S. Cohen The Biodistribution and Radiation Dosimetry of the Arg-Gly-Asp Peptide 18F-AH111585 in Healthy Volunteers J. Nucl. Med., October 1, 2008; 49(10): 1664 - 1667. [Abstract] [Full Text] [PDF]